ppm Pd-catalyzed, Cu-free Sonogashira couplings in water using commercially available catalyst precursors.

A new catalyst that derives from commercially available precursors for copper-free, Pd-catalyzed Sonogashira reactions at the sustainable ppm level of precious metal palladium under mild aqueous micellar conditions has been developed. Both the palladium pre-catalyst and ligand are commercially available, bench stable, and highly cost-effective. The catalyst is applicable to both aryl- and heteroaryl-bromides as educts. A wide range of functional groups are tolerated and the aqueous reaction medium can be recycled. An application to a key intermediate associated with an active pharmaceutical ingredient (ponatinib) is discussed

Quantifying Glomerular Filtration Rates in Acute Kidney Injury: A Requirement for Translational Success

Acute kidney injury (AKI) remains a vexing clinical problem that results in unacceptably high patient mortality, development of chronic kidney disease, and accelerated progression to end-stage kidney disease. Although clinical risks factors for developing AKI have been identified, there is no reasonable surveillance technique to definitively and rapidly diagnose and determine the extent of severity of AKI in any patient. Because patient outcomes correlate with the extent of injury, and effective therapy likely requires early intervention, the ability to rapidly diagnose and stratify patients by their level of kidney injury is paramount for translational progress. Many groups are developing and characterizing optical measurement techniques using novel minimally invasive or noninvasive techniques that can quantify kidney function independent of serum or urinary measurements. The use of both one- and two-compartment models, as well as continuous monitoring, are being developed. This review documents the need for glomerular filtration rate measurement in AKI patients and discusses the approaches being taken to deliver this overdue technique that is necessary to help propel nephrology to individualization of care and therapeutic success

Letter Regarding PBGC Request for Information on Missing Participants in Individual Account Plans, Federal Register, Vol. 78, No. 120, June 21, 2013

On August 19, 2013, the Pension Action Center wrote to the Office of the General Counsel of the Pension Benefit Guaranty Corporation in response to their request for comments on the implementation of a new program to deal with benefits of missing participants in terminating individual account plans

A new, substituted palladacycle for ppm level Pd-catalyzed Suzuki-Miyaura cross couplings in water.

A newly engineered palladacycle that contains substituents on the biphenyl rings along with the ligand HandaPhos is especially well-matched to an aqueous micellar medium, enabling valued Suzuki-Miyaura couplings to be run not only in water under mild conditions, but at 300 ppm of Pd catalyst. This general methodology has been applied to several targets in the pharmaceutical area. Multiple recyclings of the aqueous reaction mixture involving both the same as well as different coupling partners is demonstrated. Low temperature microscopy (cryo-TEM) indicates the nature and size of the particles acting as nanoreactors. Importantly, given the low loadings of Pd invested per reaction, ICP-MS analyses of residual palladium in the products shows levels to be expected that are well within FDA allowable limits

Accuracy and Reliability of Examiners’ Observations of Pre-Practice Warm-Up and FIFA 11+ Injury Prevention Program Exercises

Background: The Fédération Internationale de Football Association (FIFA) 11+ is an injury prevention program that decreases the incidence of lower extremity injuries. The purpose of the current study was to understand what specific exercises prevented injury from occurring. We thus developed and tested a form to identify these exercises. We hypothesize that trained examiners could accurately and reliably use this form to identify and record individual exercises performed during preparticipation warm-up. Methods: A repeated-measures study design was used in this investigation. After observing five prepractice warm-up videos obtained from multiple high schools, 11 examiners observed and recorded performed exercises at two different times. The videos included four soccer teams and one American football team. Accuracy, interexaminer reliability, and intraexaminer reliability were assessed. Sensitivity, specificity, accuracy, and percent agreement with a FIFA 11+ expert were measured for each exercise component. Results: The intraclass correlation coefficients between examiners and individually ranged from 0.22 to 1.00 and 0.58 to 1.00, respectively. Reliability was lowest for exercises with similar movements. The percent agreement across all examiners for individual exercises ranged from 20% to 100%. Additionally, the percent agreement between each examiner and the “gold standard” examiner was high (range, 69.6% to 90.4%). For exercises with similar movements, accuracy and reliability were considerably improved (97%) when combined into one category. Conclusion: We determined that trained examiners with different backgrounds and experience can make accurate and reliable observations of most exercises observed in warm-up programs. Using the proposed form, researchers can accurately record exercises and perform quality and fidelity assessments of warm-up exercise routines

The Internal Structure of Shock Waves

Coordinated Science Laboratory was formerly known as Control Systems LaboratoryJoint Services Electronics Program / DAAB 07-67-C-0199ONR N00015-67-A-0305-000

Pore dilation occurs in TRPA1 but not in TRPM8 channels

Abundantly expressed in pain-sensing neurons, TRPV1, TRPA1 and TRPM8 are major cellular sensors of thermal, chemical and mechanical stimuli. The function of these ion channels has been attributed to their selective permeation of small cations (e.g., Ca2+, Na+ and K+), and the ion selectivity has been assumed to be an invariant fingerprint to a given channel. However, for TRPV1, the notion of invariant ion selectivity has been revised recently. When activated, TRPV1 undergoes time and agonist-dependent pore dilation, allowing permeation of large organic cations such as Yo-Pro and NMDG+. The pore dilation is of physiological importance, and has been exploited to specifically silence TRPV1-positive sensory neurons. It is unknown whether TRPA1 and TRPM8 undergo pore dilation. Here we show that TRPA1 activation by reactive or non-reactive agonists induces Yo-Pro uptake, which can be blocked by TRPA1 antagonists. In outside-out patch recordings using NMDG+ as the sole external cation and Na+ as the internal cation, TRPA1 activation results in dynamic changes in permeability to NMDG+. In contrast, TRPM8 activation does not produce either Yo-Pro uptake or significant change in ion selectivity. Hence, pore dilation occurs in TRPA1, but not in TRPM8 channels

Feasibility and Impact of Telemonitor-Based Depression Care Management for Geriatric Homecare Patients

Objective: The objective of this study was to test the feasibility, acceptability, and preliminary clinical outcomes of a method to leverage existing home healthcare telemonitoring technology to deliver depression care management (DCM) to both Spanish- and English-speaking elderly homebound recipients of homecare services. Materials and Methods: Three stand-alone, nonprofit community homecare agencies located in New York, Vermont, and Miami participated in this study. Evidence-based DCM was adapted to the telemonitor platform by programming questions and educational information on depression symptoms, antidepressant adherence, and side effects. Recruited patients participated for a minimum of 3 weeks. Telehealth nurses were trained on DCM and received biweekly supervision. On-site trained research assistants conducted in-home research interviews on depression diagnosis and severity and patient satisfaction with the protocol. Results: An ethnically diverse sample of 48 English- and Spanish-only- speaking patients participated, along with seven telehealth nurses. Both patients and telehealth nurses reported high levels of protocol acceptance. Among 19 patients meeting diagnostic criteria for major depression, the mean depression severity was in the markedly severe range at baseline and in the mild range at follow-up. Conclusions: Results of this pilot support the feasibility of using homecare\u27s existing telemonitoring technology to deliver DCM to their elderly homebound patients. This was true for both English- and Spanish-speaking patients. Preliminary clinical outcomes suggest improvement in depression severity, although these findings require testing in a randomized clinical trial. Implications for the science and service of telehealth-based depression care for elderly patients are discussed